TRANSCRIPTIONAL REGULATOR OF PROGRAMMED CELL-DEATH ENCODED BY CAENORHABDITIS-ELEGANS GENE CES-2

THE ces (for cell-death specification) genes of the nematode Caenorhab ditis elegans the cell-death fate of individual cell types and are can didates for being the regulators of an evolutionarily conserved genera l pathway of programmed cell death(1-4). Here we present what we belie ve is the first molecular characterization of a ces gene. We cloned th e gene ces-2, which is required to activate programmed cell death in t he sister cells of the serotoninergic neurosecretory motor (NSM) neuro ns, and found that ces-2 encodes a basic region leucine-zipper (bZIP) transcription factor. The CES-2 protein is most similar to members of the PAR (proline- and acid-rich) subfamily of bZIP proteins and has DN A-binding specificity like that of PAR-family proteins. An oncogenic f orm of the mammalian PAR-family protein, hepatic leukaemia factor (HLF ), is reported to effect programmed cell death in mammalian cells(5). On the basis of these observations, we suggest that some CES-2/PAR fam ily transcription factors are evolutionarily conserved regulators of p rogrammed cell death.